Recent discovery in our laboratory revealed that 77-78% of specific-pathogen-free (SPF) cats immunized with clade B HIV-1/UCD1 vaccine were protected against subsequent FIV infection. Based on sequence analysis of HIV-1/UCD1 and FIV p24 proteins, a significant protection rate was achieved against FIV infection with a vaccine consisting of only HIV-1 p24 protein whose sequence was so distinctly different from the challenge virus. HIV-1 p24 vaccines were more effective than FIV p24 vaccines derived from pathogenic FIV strains. In fact, enhancement of FIV challenge infection was observed in the FIV p24-vaccinated cats. These findings suggest that selection of HIV-1 immunogen is essential to the development of an effective HIV-1 vaccine. Two specific aims are proposed to identify cross-protective HIV-1 p24 epitopes that may be useful as HIV-1 vaccine immunogens for humans. [unreadable] [unreadable] Specific Aim 1 will identify the cross-protective epitope(s) on HIV-1 clade B p24 using HIV/FIV-cat model and characterize the immunity induced by the protective epitopes. Specific Aim 2 will determine the relevance of the conserved protective epitopes identified in the HIV/FIV-cat model to HIV-1 vaccine development of humans. Studies will be performed to determine the HIV-1 p24 epitopes recognized by PBMC from both HIV-1-positive individuals and HIV-1 p24-vaccinated cats, understand the molecular basis of such common recognition, and evaluate if such peptides are important for eliciting vaccine protection against FIV and against SIV as a model for future human vaccine studies. These studies are the first steps toward identifying conserved protective epitopes that can prevent HIV-1 infection of humans. The innovation of the proposed studies lies in the use of the HIV/FIV-cat model to identify the cross-protective epitopes that can be used as part of HIV-1 vaccine. [unreadable] [unreadable] [unreadable]